tbuckley/cabot-search huggingface dataset:
COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis
Authors: Jonathon W. Senefeld, Massimo Franchini, Carlo Mengoli, Mario Cruciani, Matteo Zani, Ellen K. Gorman, Daniele Focosi, Arturo Casadevall, Michael J. Joyner
Journal: JAMA Network Open (2023)

Importance Patients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have been associated with monoclonal antibody-resistant SARS-CoV-2 variants and greater virulence and transmissibility of SARS-CoV-2. Thus, the therapeutic use of COVID-19 convalescent plasma has increased on the presumption that such plasma contains potentially therapeutic antibodies to SARS-CoV-2 that can be passively transferred to the plasma recipient. Objective To assess the growing number of reports of clinical experiences of patients with COVID-19 who are immunocompromised and treated with specific neutralizing antibodies via COVID-19 convalescent plasma transfusion. Data Sources On August 12, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma use in patients who are immunocompromised. Study Selection Randomized clinical trials, matched cohort studies, and case report or series on COVID-19 convalescent plasma use in patients who are immunocompromised were included. The electronic search yielded 462 unique records, of which 199 were considered for full-text screening. Data Extraction and Synthesis The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 3 independent reviewers in duplicate and pooled. Main Outcomes and Meaures The prespecified end point was all-cause mortality after COVID-19 convalescent plasma transfusion; exploratory subgroup analyses were performed based on putative factors associated with the potential mortality benefit of convalescent plasma. Results This systematic review and meta-analysis included 3 randomized clinical trials enrolling 1487 participants and 5 controlled studies. Additionally, 125 case series or reports enrolling 265 participants and 13 uncontrolled large case series enrolling 358 participants were included. Separate meta-analyses, using models both stratified and pooled by study type (ie, randomized clinical trials and matched cohort studies), demonstrated that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for the amalgam of both randomized clinical trials and matched cohort studies (risk ratio [RR], 0.63 [95% CI, 0.50-0.79]). Conclusions and Relevance These findings suggest that transfusion of COVID-19 convalescent plasma is associated with mortality benefit for patients who are immunocompromised and have COVID-19.
SERPINA12 promotes the tumorigenic capacity of HCC stem cells through hyperactivation of AKT/β-catenin signaling
Authors: Huajian Yu, Lei Zhou, Jane H.C. Loong, Ka-Hei Lam, Tin-Lok Wong, Kai-Yu Ng, Man Tong, Victor W.S. Ma, Yanyan Wang, Xiang Zhang, Terence K. Lee, Jing-Ping Yun, Jun Yu, Stephanie Ma
Journal: Hepatology (2023)

HCC is an aggressive disease with poor clinical outcome. Understanding the mechanisms that drive cancer stemness, which we now know is the root cause of therapy failure and tumor recurrence, is fundamental for designing improved therapeutic strategies. This study aims to identify molecular players specific to CD133 + HCC to better design drugs that can precisely interfere with cancer stem cells but not normal stem cell function.
Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression
Authors: Adrien Guillot, Marc Winkler, Milessa Silva Afonso, Abhishek Aggarwal, David Lopez, Hilmar Berger, Marlene S. Kohlhepp, Hanyang Liu, Burcin Özdirik, Johannes Eschrich, Jing Ma, Moritz Peiseler, Felix Heymann, Swetha Pendem, Sangeetha Mahadevan, Bin Gao, Lauri Diehl, Ruchi Gupta, Frank Tacke
Journal: Hepatology (2023)

The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis).Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts. Liver samples from alcoholic hepatitis and primary biliary cholangitis patients were used for comparison. Myeloid populations were further characterized in corresponding mouse models. Imaging, clinical, and phenotypical data were combined for multidimensional analysis. NAFLD/NASH and primary sclerosing cholangitis disease stages were associated with loss of parenchymal areas, increased ductular cell accumulation, and infiltration of immune cells. NASH patients predominantly exhibited myeloid cell accumulation, whereas primary sclerosing cholangitis patients additionally had pronounced lymphoid cell responses. Correlating to disease stage, both etiologies displayed intense IBA1 + CD16 low CD163 low macrophage aggregation in nonparenchymal areas, with a distinct spatial proximity to ductular cells. Mouse models revealed that disease-associated IBA1 + hepatic macrophages originated from bone marrow-derived monocytes. Using an unbiased, machine learning-based algorithm, IBA1 in combination with hepatocyte and ductular cell immunostaining-predicted advanced cirrhosis in human NASH, primary sclerosing cholangitis, and alcoholic hepatitis.Loss of hepatocytes and increased ductular reaction are tightly associated with monocyte-derived macrophage accumulation and represent the most prominent common immunological feature revealing the progression of NAFLD, primary sclerosing cholangitis, primary biliary cholangitis, and alcoholic hepatitis, suggesting IBA1 + CD163 low macrophages are key pathogenic drivers of human liver disease progression across diverse etiologies.
World Health Organization strategic framework for integrated control and management of skin-related neglected tropical diseases: what does this mean for dermatologists?
Authors: Rie R Yotsu, L Claire Fuller, Michele E Murdoch, Chandrakant Revankar, Yves Thierry Barogui, Venkata Ranganandha Rao Pemmaraju, Jose-Antonio Ruiz-Postigo, Daniel Argaw Dagne, Kingsley Asiedu, Roderick J Hay
Journal: British Journal of Dermatology (2022)

Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin, and includes at least nine diseases and disease groups. The World Health Organization launched the ‘Ending the neglect to attain the Sustainable Development Goals: a strategic framework for integrated control and management of skin-related neglected tropical diseases’ in June 2022, which this article summarises and sets out the way forward including guidance on how dermatologists and dermatological communities along with public health communities may support this initiative to contribute towards achieving skin care for everyone everywhere.
Effect of a Machine Learning Recommender System and Viral Peer Marketing Intervention on Smoking Cessation
Authors: Jamie M. Faro, Jinying Chen, Julie Flahive, Catherine S. Nagawa, Elizabeth A. Orvek, Thomas K. Houston, Jeroan J. Allison, Sharina D. Person, Bridget M. Smith, Amanda C. Blok, Rajani S. Sadasivam
Journal: JAMA Network Open (2023)

Importance Novel data science and marketing methods of smoking-cessation intervention have not been adequately evaluated. Objective To compare machine learning recommender (ML recommender) computer tailoring of motivational text messages vs a standard motivational text–based intervention (standard messaging) and a viral peer-recruitment tool kit (viral tool kit) for recruiting friends and family vs no tool kit in a smoking-cessation intervention. Design, Setting, and Participants This 2 ×2 factorial randomized clinical trial with partial allocation, conducted between July 2017 and September 2019 within an online tobacco intervention, recruited current smokers aged 18 years and older who spoke English from the US via the internet and peer referral. Data were analyzed from March through May 2022. Interventions Participants registering for the online intervention were randomly assigned to the ML recommender or standard messaging groups followed by partially random allocation to access to viral tool kit or no viral tool kit groups. The ML recommender provided ongoing refinement of message selection based on user feedback and comparison with a growing database of other users, while the standard system selected messages based on participant baseline readiness to quit. Main Outcomes and Measures Our primary outcome was self-reported 7-day point prevalence smoking cessation at 6 months. Results Of 1487 participants who smoked (444 aged 19-34 years [29.9%], 508 aged 35-54 years [34.1%], 535 aged ≥55 years [36.0%]; 1101 [74.0%] females; 189 Black [12.7%] and 1101 White [78.5%]; 106 Hispanic [7.1%]), 741 individuals were randomly assigned to the ML recommender group and 746 individuals to the standard messaging group; viral tool kit access was provided to 745 participants, and 742 participants received no such access. There was no significant difference in 6-month smoking cessation between ML recommender (146 of 412 participants [35.4%] with outcome data) and standard messaging (156 of 389 participants [40.1%] with outcome data) groups (adjusted odds ratio, 0.81; 95% CI, 0.61-1.08). Smoking cessation was significantly higher in viral tool kit (177 of 395 participants [44.8%] with outcome data) vs no viral tool kit (125 of 406 participants [30.8%] with outcome data) groups (adjusted odds ratio, 1.48; 95% CI, 1.11-1.98). Conclusions and Relevance In this study, machine learning–based selection did not improve performance compared with standard message selection, while viral marketing did improve cessation outcomes. These results suggest that in addition to increasing dissemination, viral recruitment may have important implications for improving effectiveness of smoking-cessation interventions. Trial Registration ClinicalTrials.gov Identifier: NCT03224520
Inflammatory induration in hidradenitis suppurativa and application to severity assessment
Authors: Gretchen Bellefeuille, Briana Paiewonsky, Bisma Khalid, Rebecca L Freese, Michelle A Lowes, Joslyn S Kirby, Afsaneh Alavi, Noah Goldfarb
Journal: British Journal of Dermatology (2022)

Skin thickness, as known as inflammatory induration, is a component in several HS grading instruments including the HASI and HASI-R. This study sought to evaluate how thickest lesion measurement (mm) corresponds to HS severity. This study demonstrates that inflammatory induration has moderate association with HS severity, thickest lesion measurement (mm) demonstrates known-validity across Hurley stages, and cut-offs for thickest lesion measurement (mm) were determined for inflammatory induration grading for the purpose of HASI-R training.
The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes
Authors: Mette Louise Trempenau, Mikkel Bruhn Schuster, Sachin Pundhir, Mafalda Araujo Pereira, Adrija Kalvisa, Marta Tapia, Jinyu Su, Ying Ge, Bauke de Boer, Alexander Balhuizen, Frederik Otzen Bagger, Pavel Shliaha, Patrycja Sroczynska, Julian Walfridsson, Kirsten Grønbæk, Kim Theilgaard-Mönch, Ole N. Jensen, Kristian Helin, Bo T. Porse
Journal: Leukemia (2023)

Epigenetic regulators are frequently mutated in hematological malignancies including acute myeloid leukemia (AML). Thus, the identification and characterization of novel epigenetic drivers affecting AML biology holds potential to improve our basic understanding of AML and to uncover novel options for therapeutic intervention. To identify novel tumor suppressive epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML. This identified the Histone 3 Lysine 4 (H3K4) demethylase KDM5C as a tumor suppressor, and we show that reduced Kdm5c/KDM5C expression results in accelerated growth both in human and murine AML cell lines, as well as in vivo in Cebpa mutant and inv(16) AML mouse models. Mechanistically, we show that KDM5C act as a transcriptional repressor through its demethylase activity at promoters. Specifically, KDM5C knockdown results in globally increased H3K4me3 levels associated with up-regulation of bivalently marked immature genes. This is accompanied by a de-differentiation phenotype that could be reversed by modulating levels of several direct and indirect downstream mediators. Finally, the association of KDM5C levels with long-term disease-free survival of female AML patients emphasizes the clinical relevance of our findings and identifies KDM5C as a novel female-biased tumor suppressor in AML.
Introducing Norah Terrault, MD, MPH, Our 2023 AASLD President
Authors: Marion G. Peters, Jennifer C. Lai
Journal: Hepatology (2023)

1Department of Medicine, Northwestern University, Chicago, Illinois, USA 2Department of Medicine, University of California, San Francisco, San Francisco, California, USA Correspondence Jennifer C. Lai, 513 Parnassus Avenue, UCSF Box 0538, San Francisco, CA 94143, USA. Email: [email protected]
Checkpoint inhibitor hepatotoxicity: pathogenesis and management
Authors: Morven Cunningham, Rohit Gupta, Marcus Butler
Journal: Hepatology (2023)

Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, has been a paradigm shift in cancer therapeutics, producing durable cancer responses across a range of primary malignancies. ICI drugs increase immune activity against tumor cells, but may also reduce immune tolerance to self-antigens, resulting in immune-mediated tissue damage. ICI-associated hepatotoxicity usually manifests as hepatocellular enzyme elevation and may occur in 2%–25% of ICI-treated patients. Although ICI-associated hepatotoxicity is clinically and pathologically distinct from idiopathic autoimmune hepatitis, our understanding of its pathogenesis continues to evolve. Pending greater understanding of the pathophysiology, mainstay of management remains through treatment with high-dose corticosteroids. This approach works for many patients, but up to 30% of patients with high-grade hepatotoxicity may not respond to corticosteroids alone. Furthermore, atypical cholestatic presentations are increasingly recognized, and rare cases of fulminant hepatitis due to ICI hepatotoxicity have been reported. Optimal management for these challenging patients remains uncertain. Herein, we review the current understanding of pathogenesis of ICI-associated toxicities, with a focus on hepatotoxicity. Based on the existing literature, we propose evolving management approaches to incorporate strategies to limit excess corticosteroid exposure, and address rare but important presentations of cholestatic hepatitis and fulminant liver failure. Finally, as ICI hepatotoxicity frequently occurs in the context of treatment for advanced malignancy, we review the impact of hepatotoxicity and its treatment on cancer outcomes, and the overall safety of re-challenge with ICI, for patients who may have limited treatment options.
Telehealth interventions in patients with chronic liver diseases: A systematic review
Authors: Abdullah A. Muftah, Chaitra Banala, Taaj Raasikh, Taher Jamali, Gabriel Bustamante, George Cholankeril, Fasiha Kanwal, Avegail Flores, Ruben Hernaez
Journal: Hepatology (2023)

Background and Aim: Telehealth interventions may improve access to care, disease-specific, and quality outcomes in chronic liver diseases (CLDs). We aimed to systematically evaluate outcomes of telehealth interventions in CLDs. Materials and Methods: We used key terms and searched PubMed/EMBASE from inception to January 10, 2022. Two authors independently screened abstracts. Disagreements were resolved by a third reviewer. We included any type of CLD, including posttransplant patients, and extracted outcomes as defined by authors for each etiology of CLD (sustained virological response in HCV or weight loss in NAFLD). Meta-analysis was not performed because of the heterogeneity of data. Quality assessment was performed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for clinical trials. Results: Of 4250 studies screened, 43 met the inclusion criteria. Of these, 28 reported HCV treatment outcomes. All studies showed no statistically significant differences between sustained virological response rates in TH groups compared with control groups or historic cohorts. Eight studies evaluating liver transplant-related processes and outcomes demonstrated improved rates of transplant evaluation and referrals and decreased short-term readmission rates. Three randomized controlled trials and 1 observational study on NAFLD showed improved weight loss outcomes. One retrospective study showed reduced mortality risk in CLD patients with at least 1 TH encounter. Conclusions: TH interventions in patients with CLDs consistently show equivalent or improved clinical outcomes compared with traditional encounters. TH in CLDs can bridge the gap in access while maintaining the quality of care for underserved populations.
Vaccination Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten — United States, 2021–22 School Year
Authors: Ranee Seither, Kayla Calhoun, Oyindamola Bidemi Yusuf, Devon Dramann, Agnes Mugerwa-Kasujja, Cynthia L. Knighton, Carla L. Black
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

State and local school vaccination requirements protect students and communities against vaccine-preventable diseases (1). This report summarizes data collected by state and local immunization programs* on vaccination coverage and exemptions to vaccination among children in kindergarten in 49 states† and the District of Columbia and provisional enrollment or grace period status for kindergartners in 27 states§ for the 2021-22 school year. Nationwide, vaccination coverage with 2 doses of measles, mumps and rubella vaccine (MMR) was 93.5%¶; with the state-required number of diphtheria, tetanus, and acellular pertussis vaccine (DTaP) doses was 93.1%**; with poliovirus vaccine (polio) was 93.5%††; and with the state-required number of varicella vaccine doses was 92.8%.§§ Compared with the 2020-21 school year, vaccination coverage decreased 0.4-0.9 percentage points for all vaccines. Although 2.6% of kindergartners had an exemption for at least one vaccine,¶¶ an additional 3.9% who did not have an exemption were not up to date with MMR. Although there has been a nearly complete return to in-person learning after COVID-19 pandemic-associated disruptions, immunization programs continued to report COVID-19-related impacts on vaccination assessment and coverage. Follow-up with undervaccinated students and catch-up campaigns remain important for increasing vaccination coverage to prepandemic levels to protect children and communities from vaccine-preventable diseases.
Integrating Phylogenetics With Intron Positions Illuminates the Origin of the Complex Spliceosome
Authors: Julian Vosseberg, Daan Stolker, Samuel H A von der Dunk, Berend Snel
Journal: Molecular Biology and Evolution (2023)

Eukaryotic genes are characterized by the presence of introns that are removed from pre-mRNA by a spliceosome. This ribonucleoprotein complex is comprised of multiple RNA molecules and over a hundred proteins, which makes it one of the most complex molecular machines that originated during the prokaryote-to-eukaryote transition. Previous works have established that these introns and the spliceosomal core originated from self-splicing introns in prokaryotes. Yet, how the spliceosomal core expanded by recruiting many additional proteins remains largely elusive. In this study, we use phylogenetic analyses to infer the evolutionary history of 145 proteins that we could trace back to the spliceosome in the last eukaryotic common ancestor. We found that an overabundance of proteins derived from ribosome-related processes was added to the prokaryote-derived core. Extensive duplications of these proteins substantially increased the complexity of the emerging spliceosome. By comparing the intron positions between spliceosomal paralogs, we infer that most spliceosomal complexity postdates the spread of introns through the proto-eukaryotic genome. The reconstruction of early spliceosomal evolution provides insight into the driving forces behind the emergence of complexes with many proteins during eukaryogenesis.
Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies
Authors: Niels A. D. Guchelaar, Bo J. Noordman, Stijn L. W. Koolen, Bianca Mostert, Eva V. E. Madsen, Jacobus W. A. Burger, Alexandra R. M. Brandt-Kerkhof, Geert-Jan Creemers, Ignace H. J. T. de Hingh, Misha Luyer, Sander Bins, Esther van Meerten, Sjoerd M. Lagarde, Cornelis Verhoef, Bas P. L. Wijnhoven, Ron. H. J. Mathijssen
Journal: Drugs (2023)

Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease.